Study shows high response rate even with imperfect adherence

SAN FRANCISCO -- Most people who inject illicit drugs can complete treatment for hepatitis C and achieve a cure using direct-acting antiviral (DAA) therapy, even if they do not have perfect adherence, according to study results presented here.

People who eventually finished at least 8 weeks of an intended 12-week course of sofosbuvir/velpatasvir (Epclusa) had a high likelihood of achieving sustained virological response (SVR), even if they had gaps in treatment.

"Our data demonstrate that people who inject drugs can achieve SVR at comparable rates to non-drug using populations, even if adherence is imperfect," said Elana Rosenthal, MD, of the Institute of Human Virology at the University of Maryland in Baltimore. "With access to hepatitis C treatment and culturally competent care, hepatitis C elimination in people who inject drugs is an achievable target."

Rosenthal presented results from the ANCHOR study, which evaluated hepatitis C treatment at a harm reduction drop-in center in Washington, D.C., at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).

Hepatitis C virus (HCV) is readily transmitted via shared syringes, and people who inject drugs have a high prevalence of HCV infection worldwide. Widespread treatment of people who inject drugs is key to the elimination of hepatitis C, but this population has often been denied access to highly effective DAAs due to concerns about poor adherence or reinfection after being cured.

But these fears appear to be unfounded. A recent meta-analysis by Jason Grebely, PhD, of the Kirby Institute at the University of New South Wales, and colleagues found that across eight studies of people who report recent injection drug use, 97% completed DAA treatment and 87% achieved SVR. Less is known, however, about outcomes in real-world settings.

Study Details

The ANCHOR study enrolled 100 participants with chronic HCV infection, opioid use disorder, and injection drug use within the past 3 months. Three quarters were men, more than 90% were black, and the median age was 57. A third had cirrhosis, but those with decompensated liver disease were excluded.

At the time of screening, 58% of participants said they injected opioids at least once daily, a third had shared injection equipment during the past 3 months, and 40% reported hazardous drinking. Only a third were on medication-assisted treatment to manage addiction. About one half of participants reported being homeless or unstably housed, 92% had a history of incarceration, and the same proportion had no income or only government benefits.

"This is an incredibly marginalized population," Rosenthal told reporters at an AASLD press conference. "Our goal when enrolling the study was to take any person with an opioid use disorder and ongoing injection drug use who was interested in treatment. We did not preferentially enroll patients who we thought would be most likely to be cured, and we did not exclude patients who seemed unlikely to adhere to treatment."

All participants were prescribed sofosbuvir/velpatasvir for 12 weeks. This pangenotypic regimen is effective against all genotypes of HCV. Medication was dispensed monthly in bottles containing 28 pills.

Rosenthal's team measured HCV viral load at week 4 as an early marker of adherence and asked about interruptions in treatment, the number of pill bottles finished, and, for those who finished all three bottles, when the last pill was taken.

Overall adherence was good. Attendance at the 4-week follow-up visit was 88%, falling to 70% at the 12-week visit but returning to 88% at the final 24-week visit. By week 4, 89% had undetectable HCV viral load (<200 IU/ml).

The overall SVR rate was 78% for the 93 participants in an intention-to-treat analysis who completed 12 weeks of post-treatment follow-up. Of the remainder, 10% experienced virological treatment failure, 9% were lost to follow-up, and one person died. In a per-protocol analysis of the 82 individuals who remained in the study, the SVR rate was 89%.

The likelihood of achieving SVR was not affected by daily injection, unstable housing, hazardous drinking, or not receiving medication-assisted addiction treatment. But viral load at week 4 did predict who would go on to be cured: Among those with undetectable HCV RNA at week 4, 86% achieved SVR, compared with only 25% of those who had detectable virus at that visit.

Most participants (87%) finished all three bottles of medication, with seven more taking at least two full bottles. The intention-to-treat SVR rates were 85% for the first group and 71% for the second. But none of the six people who finished less than two bottles were cured.

Thirteen people did not complete treatment, 21 finished on time, and 46 finished after the planned 12 weeks. The intention-to-treat SVR rate was highest in the on-time group (95%), but even those who took longer to finish had a high likelihood of being cured (88%).

"As long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates," Rosenthal said.

Thirteen participants reported treatment interruptions at some point during the 12-week course. Nine of these gaps lasted 10 days or longer, with the longest being 70 and 196 days. Reasons for treatment interruption included medications being lost or stolen, hospitalization, incarceration, and entering inpatient drug treatment.

Treatment interruptions did not consistently predict treatment failure. The six individuals with gaps of 3 to 10 days were all cured, as were those with the 70-day and 196-day interruptions. However, three people with gaps of 14, 15, and 30 days did not achieve SVR. Taken together, people with no interruptions had an SVR rate of 86%, compared with 67% for those with any interruptions.

In summary, people who inject drugs have high rates of treatment completion and cure, the researchers concluded. Imperfect adherence did not seem to affect the likelihood of SVR, even in people with interruptions in treatment, but completion of at least 8 weeks of sofosbuvir/velpatasvir was important for achieving a cure.

"The ANCHOR study demonstrates that concerns about adherence, housing status, drug use frequency, and being on medication for opioid use disorder are not likely to influence treatment outcome and should not be used to justify exclusion from treatment in this population," Rosenthal told reporters. In fact, she added, people who inject drugs should be given high priority because injection drug use is the primary risk factor for HCV transmission in the United States.

"Particularly among hepatologists -- less so among infectious disease specialists -- they've had a bias against treating people who inject drugs because of concern about reinfection or adherence," the moderator of the press conference, Jordan Feld, MD, of the Toronto Centre for Liver Disease, told MedPage Today. "This shows that even in this highly marginalized population, you can achieve high cure rates. In addition to the benefit to these individuals, you have the societal public health benefit of reducing transmission, and studies show that treating people who inject drugs is cost-effective. [Denying treatment] is just a morality issue -- it has nothing to do with science," he said.

Rosenthal did not disclose relevant financial relationships.

Feld disclosed relationships with companies including AbbVie, Gilead, and Merck.

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